1. Field of the Invention
The present invention relates to a process of preparing (3R,4R)-3-hydroxy-4-hydroxymethyl-4-butanolide.
2. Description of the Related Art
In recent years, chemical compounds containing natural occurring sugar and sugar-analog compounds have been drawn attention as useful physiologically active ingredients in a fine chemical field such as pharmaceutical agents and agricaltural agents. Many studies have been widely conducted on synthesis of the above-mentioned chemical compounds.
Examples of the above-mentioned compounds include hydroxylactone and the like which are not only physiologically active compounds but also sugar-analog compounds to be used as starting materials for various useful chemical compounds.
(3R,4R)-3-hydroxy-4-hydroxymethyl-4-butanolide represented by the following formula [1] is a chemical compound belonging to hydroxylactones and a noteworthy compound by virtue of to its usefulness. ##STR1##
Basic physiological studies with regard to physiological properties of the above-mentioned lactone have been conducted since the lactone is expected to be used as an appetite suppressing ingredient (an appetite satisfying ingredient) and application of the lactone to pharmaceutical agents and agricultural agents has been desired [T. Sakata, Brain Res. Bull., 25(6), 969-74, (1990)]. On the other hand, the lactone is also useful as a starting material for synthesis of other useful chemical compounds. For example, 2-deoxy-D-lyxose known as a rare sugar compound can be obtained by a process in which lactol is formed by reduction of a carbonyl group of the 1-position of the lactose. Thus obtained rare sugar can be used as a raw material of a sugar part of AZT (3'-azido-3'-deoxythymidine), which is a nucleic acid derivative known as an anti-AIDS drug [G. W. J. Fleet, J. C. Son, and A. E. Derome, Tetrahedoron, 44, 625, (1988)]. The lactone can be used as an aroma, for example, as an additive to improve aroma and taste of cigarettes. The lactone can be further used as a starting material for synthesizing other aromas (Published Patent "5-O-substituted-2-deoxyxylono-1,4-lactone and a process of preparing the same", Published Unexamined Japanese Patent Application No. 61-65878).
As described above, (3R,4R)-3-hydroxy-4-hydroxymethyl-4-butanolide is a useful hydroxylactone expecting a wide range usage. However, the lactone is rarely obtained from natural source so as to totally depend on synthetic methods.
There are five representative conventional methods.
1) 2,3-O-isopropylidene-D-glyceraldehyde is reacted with enolate prepared by trihalogenoacetate and Grignard reagent, thereby to increase carbon numbers of the glyceraldehyde. Then, lactone is synthesized through a process of dehalogenation etc. This method includes four processes and an overall yield is 16% [B. Rague, Y. Chapleur, and B. Castro, J. Chem. Soc. Perkin Trans. I, 2063, (1982)]. PA1 2) 2,3-O-isopropylidene-D-glyceraldehyde is reacted with sulfanylidene derivative (Me.sub.2 S=CHCONR.sub.2) which is sulfurylide, thereby to increase carbon numbers of glyceraldehyde. The resultant product, 2,3-epoxyamide is then subjected to reductive ring-opening, followed by lactonization. This method includes three processes and an overall yield is about 10% [M. V. Fernandez, P. D. Lanes, and F. J. L. Herrera, Tetrahedron, 46, 7911, (1990)]. PA1 3) 2,3-O-isopropylidene-D-glyceraldehyde is reacted with diazoacetate, thereby to increase carbon numbers of the glyceraldehyde. The resultant product .beta.-ketoester and 2-diazo-3,4,5-trihydroxypentanoate derivative are subjected to a reduction reaction, followed by lactonization. This method includes three processes and an overall yield is 12 to 16% [F. J. L. Herrera, M. V. Fernandez, and S. G. Claros, Tetrahedron, 46, 7165 (1990)]. PA1 4) 2,3-O-isopropylidene-D-glyceraldehyde is reacted with organic lithium reagent (LiCH.sub.2 COOBu-t), thereby to increase carbon numbers of glyceraldehyde. The resultant product, 3,4,5-trihydroxypentanoate is subjected to lactonization [G. A. Danilova, V. I. Mel'nikova, and K. K. Pivnitsky, Tetrahedron Lett., 27, 2489 (1986)]. PA1 5) D-galactose is treated with alkali under high pressure to obtain D-lyxono-1,4-lactone. The resultant product lactone is subjected to bromination and debromination of the 2-position thereof, thereby to obtain a desired lactone which is a deoxy from at the 2-position. This method includes 4 processes and an overall yield is 38% or less [K. Bock, I. Lundt, and C. Pedersen, Carbohydr. Res., 90, 17, (1981); and W. J. Humphlett, Carbohydr. Res., 4, 157, (1967)]. PA1 Process (b): An iodo-group of an .alpha.-configuration is added to the double bond at 4-position of a compound represented by formula [3]and an acyloxy ion of a .beta.-configuration is added to the double bond at 3-position of a compound represented by formula [3] in a trans form, followed by subjecting an acyloxy group to hydrolysis in the presence of a base, thereby to regioselectively and stereoselectively prepare the chemical compound represented by formula [4] having an oxirane ring of a .beta.-configuration. ##STR8## where R is an alkyl group or an aryl group. PA1 Second, the obtained chemical compound [7] is hydrolyzed to form alkoxide at the 3-position. An iodo-group of the 4-position is removed by intramolecular nucleophilic displacement reaction of the alkoxide, thereby to obtain an oxirane ring of a .beta.-configuration. ##STR11## PA1 1) The oxidation with dimethyl sulfoxide in combination with dicyclohexylcarbodiimide, acetic anhydride, phosphorous pentoxide, trifluoroacetic anhydride, oxalyl chloride, halogen, and the like. PA1 2) The oxidation with chromate such as chromium oxide (VI) represented by John's oxidation, dichromate, chromium oxide-pyridine complex (Collins reagent), pyridinium chlorochromate (PCC), pyridinium dichlorochromate (PDC), and the like. PA1 3) The oxidation with manganese dioxide. PA1 4) The oxidation with hypohalite, halic acid, and the like. PA1 5) The oxidation with Oppenauer oxidation or 2,3-dichloro-5,6-dicyano-p-benzoquinone. PA1 6) The oxidation with a transition metal catalyst such as ruthenium tetraoxide, a platinum catalyst, and a palladium catalyst. PA1 7) The oxidation with silver carbonate, copper (II) salt, lead tetraacetate, and the like.
The above methods 3) and 4) have low yields of (3R,4R)-3-hydroxy-4-hydroxymethyl-4-butanolide since an intermediate compound having a desired configuration is rarely obtained due to low stereoselectivity of a hydroxyl group formed at the 3-position by an increasing-carbon-number reaction of 2,3-O-isopropylidine-D-glyceraldehyde. This process further requires additional two processes to obtain a raw material of 2,3-0-isopropylidene-D-glyceraldehyde from D-mannitol with the result that a yield is further decreased [R. Dumont and H. Pfander, Helv. Chim. Acta, 66, 814, (1983)].
In the method 4), on the other hand, 3-hydroxy-4-hydroxymethyl-4-butanolide is synthesized as a synthetic intermediate. Therefore, stereoselectivity of a hydroxyl group of the 3-position of the above compound is not a matter of consideration. Since a diastereoisomer simultaneously produced at the 3-position of the above compound is difficult to separate, the next reaction is carried out without separating the diasteroisomer. In process 5), 3-hydroxy-4-hydroxymethyl-4-butanolide is used as an synthetic intermediate. As s result, a reaction is proceeded without diastereoisomer isolation. Process 5) is difficult to operate since high pressure is required as a reaction condition. Therefore, it is very difficult to selectively obtain (3R,4R)-3-hydroxy-4-hydroxymethyl-4-butanolide.
As is apparent from the foregoing, a convenient synthetic method has not been attained to prepare the desired compound of the present invention with a high stereoselectivity in a high yield.